Pneumococcal pneumoniaJ13

Diplococci in the blood of rabbits were first described in the late 19th century by Louis Pasteur (Paris) and Georg Sternberg (American army doctor). In the years 1884-1886, several authors succeeded in independently detecting Diplokokkus pneumoniae.

By pneumococcal pneumonia we understand an acute inflammation of the pulmonary alveoli. It is typically limited to one lobe of the lung, but occurs in more than one lobe of the lung to about 30%.

Streptococcus pneumoniae: There are over 40 serotypes (indicated by a number) with over 90 different capsular polysaccharide types (indicated by a number + letters). This capsule protects the pneumococci from phagocytosis by alveolar macrophages. There is no cross-immunity within the individual serotypes. Transmission occurs aerogenically.

Pneumococcus is the most common pathogen causing ambulatory acquired pneumonia (CAP) worldwide and pneumococcal disease is the most fatal infectious disease in industrialized countries.

In infants, up to 60% of pneumococci are found in the mucous membranes of the nasopharynx; in adults, only about 10% of pneumococci are detectable. However, the number increases again with age due to the weaker immune system. In adults without infant contact, only 5 % of diplococci are found in the nasopharynx.

Pneumococci are not obligatory pathogens, since normally an intact immune system prevents the disease.

However, a disease is usually not triggered by the serotypes found in the patient's own nasopharynx, but rather by infection with foreign serotypes via droplet infection.

Risk factors for pneumococcal pneumonia are:

• age (children and elderly people have a significantly higher incidence)
• congenital and acquired immunodeficiencies
• chronic diseases (such as alcoholics, chronic heart or lung diseases, e.g. splenectomy)

The pneumococci reach the deeper respiratory tract by inhalation (droplet infection). Due to the outer polysaccharide capsule, the cocci cannot be phagocytized by the alveolar macrophages, as is usually the case when pathogens penetrate deeply.

• sudden onset from a state of well-being with high fever and chills
• cough, nasal breathing, in case of involvement of the pleura respiratory pain in the thorax
• unspecific symptoms such as fatigue, headache, myalgias, arthralgias
• in approx. 20 % also gastrointestinal symptoms such as nausea, vomiting, diarrhoea
• reddish-brown sputum from the 2nd day (contains abundant granulocytes)
• in elderly patients, the disease can often manifest itself exclusively as confusion and malaise; fever, chills and cough are completely absent

Lobar pneumonia progresses in 4 stages:

1st stage: (for about 24 h) so-called "Anschoppung"; the alveoli are filled with exudate; auscultatorically there is a crepitatio indux (due to lack of consolidation of the infiltrate).

2nd stage: (2nd-3rd day) so-called red hepatisation; fibrin threads and erythrocytes stain the lungs dark red and give them a liver-like consistency (hepatisation).

3rd stage: (4th-6th/8th day) so-called grey-yellow hepatisation due to leucocyte infiltration; climax of the disease.

4th stage: (after the 8th day) so-called lysis; dissolution of the exudate by granulocyte decay; expectoration of purulent sputum; auscultatory crepitatio redux (alveoli are air-containing again).

The stages described above are rarely observed today, since antibiotics are usually administered at an early stage.

The C(U)RB-65 score is used to quantify the severity of the disease:

• Confusion
• Urea> 7 mmol/l
• Respiratory rate > 30/min
• Blood pressure: systolic < 90mmHg or diastolic <60mmHg
• Age 65 years or older

From 2 of a maximum of 4 (5) points, patients should be hospitalized in any case.

• 0 points: lethality 1-2%
• 1-2 points: lethality 13
• 3-4 (5) points: lethality > 31 %.

Caveat: cannot always be used with certainty in multimorbid patients, as the prognosis is often unfavourable despite a low score. The mortality of patients who were initially treated in the normal ward and transferred to the intensive care unit because of a deterioration in their condition is higher than that of patients who were immediately treated with intensive care. The evaluation therefore required should be done by recording the minor criteria of the modified ATS score. Modified ATS score:

Major criteria:

• Need for intubation and mechanical ventilation.
• Need for administration of vasopressors > 4 hours (septic shock).

Minor criteria:

• severe acute respiratory failure (paO2 / FiO2 <250)
• multilobular infiltrates on chest x-ray
• systolic blood pressure < 90 mmHg
• disturbance of consciousness
• respiratory rate > 30/min
• acute renal failure
• leukopenia
• thrombocytopenia
• Hypothermia

If at least 1 major criterion or 2 minor criteria are positive, immediate intensive medical treatment is recommended. The sensitivity is 69%, the specificity 97%, the predictive value 94%.

Sharp-edged shading limited to one lobe (in approx. 30 % more than 1 lobe is affected)

Leucocytosis

CRP in the beginning mostly normal, also Procalcitonin

Left shift

Pathogen detection in blood, sputum and bronchial lavage possible. The germs can be cultivated easily. In the Gram staining they can be recognized as positive diplococci. The sensitivity and specificity of both the Gram stain and the culture are subject to large fluctuations in sputum. Even in the case of a proven bacteraemic pneumococcal infection, at most 50 % pneumococci are detectable in sputum.

Pneumococcal antigen is detectable in blood, sputum and urine. For the rapid detection of pneumococci, a urine test, e.g. Binaxnow Streptococcus pneumoniae, is available, which gives the result after only 15 minutes. The sensitivity is between 67-82%, the specificity is about 97%.

Auscultation:

• fine to medium bubble rales
• Bronchial breathing
• positive bronchophony
• positive vocal fremitus

Main diagnostic criterion:

• New onset or progressive infiltrate on radiograph in 2 planes.

Secondary diagnostic criteria:

• Pneumonia typical auscultation findings, positive bronchophony/voice fremitus.
• fever > 38.5°C (measured rectally) or hypothermia
• purulent sputum
• leukocytosis or leukopenia
• Pathogen detection (sputum, bronchial secretions, pleural punctate, blood culture).

There must be 1 major criterion plus 2 minor criteria to establish a diagnosis of pneumonia.

• Lung abscess
• Pleuritis
• Pleural effusion
• Pleural empyema (drainage)
• Sepsis
• Shock
• Multiorgan Failure
• Acute aggressive lung failure (ARDS)

General measures:

• Physical protection (if necessary heparinization and / or antithrombosis stockings)
• adequate fluid intake (important in case of fever and for secretolysis)
• NaCl inhalations
• in case of hypoxia oxygen by nasal probe

Pneumococci are sensitive to penicillin. However, resistances occur more and more frequently, which vary greatly from region to region. The USA has the highest resistance rate with > 50 %, in Spain, Hungary and France it is up to 50 % and in Germany < 10 % and is therefore negligible.

The means of choice is

• Amoxicillin (3x1 g/d p.o.)

In case of known penicillin allergy

• fluoroquinolone(moxifloxacin 1x400 mg/d or levofloxacin 1x500-750 mg/d), with moxifloxacin being more effective.
• Clindamycin 600-1200 mg/d p.o. in single doses every 6 hours (90% effective) or azithromycin 1x500 mg/d p.o., then 250-500 mg/d p.o.) and clarithromycin 1x500-750 mg/d p.o. (both 80 % effective) are subordinate alternatives.

For patients with previous lung diseases (severe COPD, bronchiectasis etc.), betalactam is recommended as the drug of choice, e.g.

• Amoxicillin/Clavulanic acid 2x2g/d p.o.
• alternatively fluoroquinolone e.g. Levofloxacin 1x750 mg/d p.o..

Therapy for in-patients

• Patients should receive amoxicillin/clavulanic acid 3-4x2.2 g/d plus macrolide e.g. azithromycin 1x500 mg/d.
• Patients with the risk of an additional Pseudomonas aeruginosa infection should receive a pseudomonas effective penicillin plus beta-lactamase inhibitor piperacillin/tazobactam 3-4x4.5g plus fluoroquinolone e.g. levofloxacin 1-2x500mg/d

Therapy for in-patients in intensive care units

• Betalactam e.g. cefotaxime 1-2 g i.v. every 8 h, ceftriaxone 1x2 g/d i.v. or ampicillin/sulbactam 2g i.v. every 8 h

+

• Macrolide antibiotic e.g. azithromycin (1x1 g i.v., then 1x500 mg/d) or fluoroquinolone such as moxifloxacin 1x400 mg/d i.v.

In in-patients the antibiosis is usually given intravenously, with the exception of fluoroquinolones.

Duration of therapy: There are different indications, as the optimal duration of treatment is not known. Most recommendations speak of a continuation of the antibiosis for at least 3-5 days after defibrillation.

Prophylaxis/prevention: The most important measure for prevention is vaccination against pneumococcus. The protective effect of active immunization is about 70%. The vaccination can be administered both s.c. and i.m.

A vaccine against pneumococci was first developed in 1945 with four capsule antigens. In the 70s a vaccine with 14 antigens was added. The current variant with 23 vaccine strains (23-valent polysaccharide vaccine PPSV23) was developed in 1983. It contains antigens from 23 different pneumococcal types, which in turn are responsible for 90 percent of pneumococcal diseases in adults.

In 2001, the conjugate vaccine PCV13 appeared on the market.

There are 2 different vaccines for adults:

• 23-valent polysaccharide vaccine PPSV23 (trade name Pneumovax® 23)
• 13-valent conjugate vaccine PCV13 (trade name Prevenar® 13).

Differences between the vaccines: Although PPSV 23 contains more serotypes than PCV13, PPSV 23 only stimulates B cells and not T cells. As a result, no immunological memory can be built. This then leads to depletion of the B-cell pool.

Particularly in older people, but also in immunocompromised people, specific new naive B cells can only form very slowly, which has been demonstrated in several studies by reduced antibody formation. This effect is called hyporesponsiveness. Only 10 years after the first vaccination this phenomenon is no longer detectable.

The Standing Vaccination Commission (STIKO) recommends that all adults over the age of 60 should be vaccinated in general. The vaccine PPSV23 should be used, as it protects against 23 of a total of more than 90 serotypes.

A general booster is not recommended for healthy persons and should be decided by the treating physician in each individual case.

However, in the above-mentioned persons with an increased risk of severe pneumococcal disease, a booster is recommended after at least six years (STIKO with reference to the technical information on PPSV23). Considerable side-effects are to be expected if a booster is given before the 6-year period has expired.

For immunocompromised patients and for patients with chronic diseases such as asthma, COPD, emphysema, seizure disorders, cerebral palsy and diabetes mellitus a first sequential vaccination with PCV13 is recommended. Only after 6 to 12 months vaccination with PPSV23 should be given.

In otherwise healthy patients, fever and leukocytosis regress a few days after the start of therapy. The physical findings usually last longer. The radiological changes persist the longest. They only disappear after about 4-12 weeks.

Patients who have been treated in the clinic or who are smokers should definitely have a radiological check-up after 4-6 weeks. Radiological control before 28 days has proved to be useless in studies.

If the control reveals an increase in infiltrate, a malignancy must be excluded.

Notifiable evidence of pathogens in accordance with the Infection Protection Act

(IfSG) § 7:

According to the Infection Protection Act, the detection of pneumococcus is not subject to notification in Germany. However, some federal states have introduced a reporting obligation by state regulation. This includes:

• Brandenburg
• Mecklenburg-Western Pomerania
• Saxony
• Saxony-Anhalt

In Brandenburg, Mecklenburg-Western Pomerania, Saxony and Saxony-Anhalt there is an obligation to report by name according to § 7 paragraph 1 of the Infection Protection Act in case of direct or indirect detection of Streptococcus pneumoniae.

1. Ewig S et al (2016) Treatment of adult patients with ambulatory acquired pneumonia and prevention - Update 2016 AWMF Guideline
2. Gerok et al.(2007) The Internal Medicine - Reference work for the medical specialist S 403-406
3. Herold at al. (2018) Internal Medicine S 380-381
4. Kasper DL et al (2015) Harrison's Principles of Internal Medicine S 803- 809 and S 946-954
5. Kasper DL (2015) Harrisons Internal Medicine S 977-986 and S 1158-1162
6. Loscalzo J (2010) Harrison's Lung Medicine and Intensive Care 113-125
7. Voigt et al (2006) Pneumococcal antigen test in urine - diagnostic significance in ambulatory acquired pneumonia (CAP). Pneumology 60: V107